title: Efficiency of cell-free and cell-associated virus in mucosal transmission of human immunodeficiency virus type 1 and simian immunodeficiency virus.
abstract: Effective strategies are needed to block mucosal transmission of human immunodeficiency virus type 1 (HIV-1). Here, we address a crucial question in HIV-1 pathogenesis: whether infected donor mononuclear cells or cell-free virus plays the more important role in initiating mucosal infection by HIV-1. This distinction is critical, as effective strategies for blocking cell-free and cell-associated virus transmission may be different. We describe a novel ex vivo model system that utilizes sealed human colonic mucosa explants and demonstrate in both the ex vivo model and in vivo using the rectal challenge model in rhesus monkeys that HIV-1-infected lymphocytes can transmit infection across the mucosa more efficiently than cell-free virus. These findings may have significant implications for our understanding of the pathogenesis of mucosal transmission of HIV-1 and for the development of strategies to prevent HIV-1 transmission.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dror
authors.initials: D
authors.lastname: Kolodkin-Gal
authors.forename: Sandrine L
authors.initials: SL
authors.lastname: Hulot
authors.forename: Birgit
authors.initials: B
authors.lastname: Korioth-Schmitz
authors.forename: Randi B
authors.initials: RB
authors.lastname: Gombos
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Joshua
authors.initials: J
authors.lastname: Owuor
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lifton
authors.forename: Christian
authors.initials: C
authors.lastname: Ayeni
authors.forename: Robert M
authors.initials: RM
authors.lastname: Najarian
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Yeh
authors.forename: Mohammed
authors.initials: M
authors.lastname: Asmal
authors.forename: Gideon
authors.initials: G
authors.lastname: Zamir
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D003106:Colon / Q000821:virology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000821:virology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*